The STaMINA (Stem cell Transplant for multiple Myeloma Incorporating Novel Agents) clinical trial is a randomized, multi-center, phase III study evaluating 3 different treatments after a standard autologous hematopoietic cell transplant (autoHCT): 1) a second autoHCT followed by 3 years of lenalidomide maintenance, 2) 3 years of lenalidomide maintenance only, 3) 4 cycles of chemotherapy including lenalidomide (Revlimid(r)), bortezomib (Velcade(r)), and dexamethasone (RVD) followed by 3 years of lenalidomide maintenance. This trial will enroll 750 patients from about 50 U.S. transplant centers and started accrual in June of 2010. The PRIMeR (PRognostic Immunophenotyping in Myeloma Response) ancillary study will use a comprehensive 7-color panel of plasma cell markers to differentiate between normal and abnormal (myeloma) plasma cells in about 470 patients who are enrolled in the STaMINA clinical trial from December 2010 to June 2013. To date, no studies have evaluated minimal residual disease detected by immunophenotyping in a large clinical trial comparing different treatment strategies, and no immunophenotyping studies have been reported in patients treated with novel agents. After treatments such as autoHCT which affect the production of immune proteins, the ability to detect small amounts of residual disease (myeloma) using standard disease tests is less precise. Immunophenotyping may complement or replace standard testing since it directly measures the number of abnormal (myeloma) plasma cells instead of measuring the amount of abnormal proteins secreted by the abnormal plasma cells. Immunophenotyping is a cost-effective method which can detect 1 abnormal plasma cell in 10,000 normal plasma cells, yielding a sensitivity of 0.01%. With the increase in complete response rates after modern myeloma therapy, there is an increasing need for more sensitive evaluations of disease responsiveness and monitoring disease burden over time. The overall purpose of the PRIMeR study is to measure minimal residual disease using immunophenotyping analyses in myeloma patients enrolled in the STaMINA trial to determine the association of minimal residual disease with standard myeloma tests and its ability to predict long-term survival outcomes. The PRIMeR study will perform survival analyses once the STaMINA clinical trial data have matured to determine the prognostic value of immunophenotyping in the era of novel agents and autoHCT. The PRIMeR study has the potential to change clinical practice by providing evidence of the ability of immunophenotyping to predict long-term survival and guide treatment decisions. In addition, minimal residual disease may serve as a surrogate endpoint for clinical trials, thereby speeding the development of future therapies. PUBLIC HEALTH REVELANCE: This project will compare the detection of minimal residual disease in patients with multiple myeloma who receive three different therapies under the BMT CTN STaMINA clinical Trial. The results of this study will improve the quality of disease assessment and establish a powerful surrogate marker in multiple myeloma. (End of Abstract)